Translational Molecular Pathology

Our group aims to unravel the molecular mechanisms of cancer progression and metastasis to identify new diagnostic, prognostic and therapeutic targets in cancer. By combining the knowledge and availability of human tumors in the Pathology department with the expertise of the basic molecular cell biology research group, we focus on:

Understanding: the molecular mechanisms underlying clonal cooperation and intercellular communication in heterogeneous tumors.
The role of MNK kinases in cellular stress resistance.
The role of ITGB3 in intercellular communication via extracellular vesicles in cancer metastasis (Santiago Ramon y Cajal).
The role of direct cell-cell communication via gap junctions and intercellular protrusions in cancer (Trond Aasen)
The malignant transition of Plexiform Neurofibromas (Cleofe Romagosa).

Research lines

Study of Cell Signalling pathway in human tumors. Identification of funnel factors.

We have characterized the levels of activation in Cell Signalling in a spectrum of solid tumors and correlated the levels of various factors, including mTOR and downstream proteins (p70S6K, S6, 4EBP1, eIF4E) with prognosis and grade of malignancy. Also, are being characterized, at the molecular level, the factors involved in controlling the translation cap dependent and independent in malignant tumors.

IP: Santiago Ramon y Cajal Agüeras

Study of gene expression of senescence in human tumors

The expression of mARN genes identified by Dr.R. Bernards has been studied in normal and tumor tissue of cancer patients. This study identifies for the first time, RSK4 and KIAA0828 genes as genes whose role may be relevant in cancer. The expression of these genes is being studied in protein by Western blot and immunohistochemistry. Also are characterizing the biochemical pathways where these genes may be involved.

IP: Santiago Ramon y Cajal Agüeras

Study of gene expression of senescence in human tumors

IP: Santiago Ramon y Cajal Agüeras

Expression analysis and functional elucidation of connexins and pannexins in relation to human cancer progression and malignancy.

Connexins and pannexins are structural units of gap junctions permitting direct intercellular communication. Deregulation of gap junctions is a frequent feature of carcinogenesis. We are characterizing the expression level of a variety of connexins and pannexins in primary and metastatic human tumours. In vitro we are studying how these proteins affect features related to the degree of malignancy such as migration, invasion and resistance to hypoxia. In connexin-deficient cell lines we are over-expressing specific wild-type or truncated forms of connexins and pannexins using retroviral constructs recently generated. In cell lines expressing high levels of specific connexins, we knockdown the expression levels using established lentiviral shRNA strategies. We aim to correlate connexin expression and cell communication with malignancy using a variety of well characterized assays with particular focus on colony formation, migration, invasion, epithelial-to-mesenchymal transition, changes in tumour stem cell populations, and hypoxia and drug resistance. The aim of the study is to: 1) Identify any significant correlation between the expression of various gap junction proteins and the malignancy, prognosis, chemo-resistance and overall survival in a variety of cancers 2) Gain mechanistic insight and identify direct functional roles of connexins and pannexins during tumour progression.

IP: Trond Aasen